Should COVID-19 be branded to Viral Thrombotic Fever? [ACCEPTED ARTICLES / PRELIMINARY VERSION]

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing COVID-19. Over one time-period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to Viral Hemorrhagic Fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a Viral Thrombotic Fever. This manuscript points out that SARSCoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a “thrombotic storm,” much more than a “cytokine storm.” The importance of a viral protease called main protease (Mpro) is highlighted as a key component for SARS-CoV-2 replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison of crystallographic structures.